Günter Wulff

Stoichiometric noncovalent interaction in molecular imprinting

In this review article the function of the binding site monomers in the molecular imprinting procedure is discussed. Especially, new developments towards stoichiometric noncovalent interactions are highlighted. In stoichiometric noncovalent interactions template and binding site monomer in an 1:1 molar ratio are nearly completely bound to each other. This is only possible if the association constants are considerably high (Kass < 900 M−1). Using this type of interaction in molecular imprinting no excess of binding sites is necessary and binding sites are only located inside the imprinted cavity. Since all cavities can be reloaded these polymers show high capacity (e.g., for preparative application) and are especially suited for the synthesis of catalytically active imprinted polymers. Discussed are binding site interactions based on amidines (and guanidines), multiple hydrogen bonding, charge-transfer interactions, and host–guest inclusion. The systematic investigation of the underlying binding reaction is described in detail. With low-molecular weight model substances the thermodynamics of the association can be conveniently investigated, e.g., by NMR spectroscopy.

The Synthesis, Characterization and Molecular Recognition Properties of Imprinted Microgels

Molecular imprinting, an established technique for the synthesis of insoluble crosslinked polymers with specific cavities for selective molecular recognition and catalysis, has been applied to highly crosslinked polymer nanoparticles (microgels) able to build stable solutions in appropriate solvents. Imprinted microgels with a nominal crosslinking degree above 50 wt.-% could be prepared by solution polymerization in high dilution. They were characterized by GPC, viscometry and membrane osmometry, and were found to be highly crosslinked macromolecules with a molecular weight comparable to the one of proteins. Molecular recognition experiments clearly pointed out the presence of functionalized cavities within the microgels that were able to recognize and to selectively bind sugar molecules. The experiment can be carried out in homogeneous solution, after which the microgels are conveniently separated by ultracentrifugation. Although the obtained selectivities are still low compared to the results achieved with insoluble crosslinked polymers, the success of this approach represents an important step towards the development of what might be properly described as “artificial enzymes”.

Template Imprinted Polymers for HPLC Separation of Racemates

Abstract A novel approach to the separation of enantiomers using polymeric sorbents imprinted with optically active template molecules has been examined for use in HPLC. The racemate of the template molecule can be separated whereby covalent interactions are responsible for retardation in the chromatographic process. This covalent interaction governs the overall kinetics of the separation. Increasing the reaction rate of this binding reaction by optimizing the experimental conditions improves the separation considerably. The template form of the enantioraeric mixture is thus strongly retarded and separated from the non-template form. A further substantial improvement of the chromatographic pattern is obtained by and it is remarkable that the racemic resolution of mannose n this polymer is possible although the template is different. This finding offers the possibility of the racemic resolution of underivated sugar which s not possible by other methods at the present time. It gives also an insight into the...

ABA and Star Amphiphilic Block Copolymers Composed of Polymethacrylate Bearing a Galactose Fragment and Poly(ε-caprolactone)

Novel ABA and star amphiphilic block copolymers of poly(vinyl sugars) with biodegradable hydrophobic poly(e-caprolactone) segments are presented. They were prepared by a combination of ring-opening polymerization of e-caprolactone and atom-transfer radical polymerization of methacrylate-bearing isopropylidene-protected galactose. Subsequently, the protecting groups of the sugar fragments were removed by treatment with 80% formic acid.

Enzyme-Analogue Built Polymers. XIX. Racemic Resolution on Polymers Containing Chiral Cavities

Abstract With the aid of a chiral template molecule binding groups could be placed in a highly crosslinked polymer in such a way that they are present in a chiral cavity of specific shape in a given stereochemistry. Polymers of this type possessed a high selectivity for racemic resolution of the racemate of the template. In the batch procedure separation factors α as high as 3.65 were obtained. In chromatography similar to other chromatographic racemic resolutions a slow mass transfer was observed. This is not due to resistance to intra-particle diffusion since similar polymers coated as thin layers to wide pore silica showed comparable behaviour. New chromatographic investigations on glycoldimethacrylate based polymers with high selectivity in the batch procedure are described. Systematic investigations showed that resolutions of Rs=1.2 can be obtained. At elevated temperature the separations were even better and higher retention was observed. The amount of cavities on the surface was varied and an optim...

Arylboronic acids with intramolecular B–N interaction: convenient synthesis through ortho-lithiation of substituted benzylamines

Ortho-lithiation of N, N-dimethylbenzylamine and reaction with trimethylborate gave the corresponding boronic acid in good yields. The reaction was extended to the synthesis of various aromatic boron compounds with nitrogen-containing substituents in the ortho-position, including a chiral boroxin prepared from (S)-N,N dimethyl-1-phenylethylamine. From N-methyl-benzylamine a stable boronium salt was obtained under certain conditions. The spectra of the newly synthesized compounds are discussed. Intramolecular B-N interaction by 11B NMR spectroscopy.

Microgel-supported Oxazaborolidines: Novel Catalysts for Enantioselective Reductions

Abstract Microgel-bound oxazaborolidines have been prepared and used as catalysts in the enantioselective reduction of prochiral ketones. The preparation of these soluble, crosslinked polymer molecules was accomplished by solution polymerisation. The approach involved the preparation of microgels bearing free boronic acid functionalities and their subsequent conversion to oxazaborolidines. The selectivities of these supported catalysts are in most cases comparable to those achieved with low molecular weight analogues. The advantage of the application of microgel-bound catalysts is their good solubility together with low viscosity of the solution. Reagents of this type can easily be removed by ultrafiltration and the process can be performed in a continuous mode in a membrane reactor.

Catalytically active, molecularly imprinted polymers in bead form

Polymers imprinted with a stable transition-state analogue of the carbonate ester hydrolysis have been prepared and showed remarkable catalytic activity. They have now been obtained by suspension copolymerization in bead form. The chemical structure of the polymers prepared from a complex of diphenylphosphate and a polymerisable amidine derivative copolymerised with ethylene dimethacrylate and methyl methacrylate was investigated. The effect of the composition of the monomer mixture and the polymerization conditions on morphology and porous structure was investigated. The template diphenyl phosphate was not eluted during the suspension procedure into the aqueous phase. All of the prepared copolymers are macroporous with permanent porous structure. Depending on reaction conditions, the amount of micropores and macropores and thus the accessibility of the copolymer to molecules can be varied. Catalytic activity of the prepared copolymers was tested by hydrolysis of diphenyl carbonate and diphenyl carbamate. Molecularly imprinted beads show higher imprinting selectivity than corresponding block copolymers.

Modification of amylose and investigation of its inclusion behavior

Abstract Five different amylose derivatives—hydroxypropyl, hydroxyethyl, 1,2-dihydroxypropyl, acetyl and carboxymethyl amylose—with varying degrees of substitution were investigated concerning their water solubility and their complexing ability of iodine and of several organic compounds. In general, the water solubility of all samples increased with increasing degree of substitution, whereas their complexing ability decreased. This was examined by means of UV spectroscopy and circular dichroism. The three derivatives with substituents carrying hydroxy groups showed almost equivalent behavior, while acetylated amyloses revealed much more guest-specific complexing properties. A reduced complexing ability of the carboxymethylated amyloses is attributed to an enhanced substitution at the HO-3 and HO-6 groups disturbing the helical conformation of the amylose chain and lowering the complex stability. In addition, the pH dependence was determined for two samples of carboxymethyl amylose.

Circular dichroism and ultraviolet spectroscopyof complexes of amylose

Abstract The circular dichroism of the complexes formed between slightly hydroxypropylated amylose and cyclomalto-hexaose, -heptaose, and -octaose ( α -, β-, and γ -cyclodextrin) with nine different achiral ketones and phenolphthalein has been investigated. In the complexes with the ketones, the amylose helix has a conformation with six glucose units per turn, whereas, in the complex with phenolphthalein, it has seven.